A Glucagon-Like Peptide-1 Analog Reverses the Molecular Pathology and Cardiac Dysfunction of a Mouse Model of Obesity

In addition to the previously developed recombinant modified human glucagon-like peptide 1 (rmglp1, Glypin), a recombinant modified human glucose-dependent insulinotropic peptide (RMGIP) has been obtained. A new universal reverse-phase HPLC technique has been proposed allowing quantitative analysis of rmGlp1 and rmGip separately and as part of a two-component preparation. The data show that the design of recombinant human rmGip according to the Glypine formula makes it possible to produce one-component and two-component preparations containing various rmGip and rmGlp1 protein ratios ranging from 1:0 to 20:1, using cell biomass samples mixed in predetermined proportions. Studies of human rmGip activity in a mouse model revealed reduced specific activity and signs of weak antagonistic effects. In this regard, there is a need for further study of human rmGip activity in a mouse model, including the use of alternative mouse or rat rmGip. type 2 diabetes mellitus; two-component drug, glucose-dependent insulinotropic peptide, glucagon-like peptide-1 The work was supported by the Internal Grant from National Research Center Kurchatov Institute.

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The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome

Frontiers in Pharmacology ◽

10.3389/fphar.2020.00136 ◽

2020 ◽

Vol 11 ◽

Author(s):

Shenhai Liu ◽

Zhe Jin ◽

Yiling Zhang ◽

ShiKuo Rong ◽

Wenxin He ◽

...

Keyword(s):

Mouse Model ◽

Neuronal Apoptosis ◽

Dravet Syndrome ◽

Glucagon Like Peptide ◽

Cognition Dysfunction ◽

Glucagon Like Peptide 1

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GLUCAGON-LIKE PEPTIDE-1 PROTECTS AGAINST CARDIAC DYSFUNCTION AND EXTRACELLULAR MATRIX REMODELLING IN EXPERIMENTAL DIABETES

Heart ◽

10.1136/heartjnl-2012-303148a.3 ◽

2012 ◽

Vol 98 (Suppl 5) ◽

pp. A1.3-A1 ◽

Cited By ~ 1

Author(s):

M Tate ◽

E Robinson ◽

B J McDermott ◽

D J Grieve

Keyword(s):

Extracellular Matrix ◽

Cardiac Dysfunction ◽

Experimental Diabetes ◽

Extracellular Matrix Remodelling ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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The intestine responds to heart failure by enhanced mitochondrial fusion through glucagon-like peptide-1 signalling

Cardiovascular Research ◽

10.1093/cvr/cvz002 ◽

2019 ◽

Vol 115 (13) ◽

pp. 1873-1885 ◽

Cited By ~ 3

Author(s):

Genki Naruse ◽

Hiromitsu Kanamori ◽

Akihiro Yoshida ◽

Shingo Minatoguchi ◽

Tomonori Kawaguchi ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Dysfunction ◽

Mitochondrial Dynamics ◽

Left Ventricular ◽

Mitochondrial Fusion ◽

Mitochondrial Morphology ◽

Atp Content ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

The Impact

Abstract Aims Glucagon-like peptide-1 (GLP-1) is a neuroendocrine hormone secreted by the intestine. Its receptor (GLP-1R) is expressed in various organs, including the heart. However, the dynamics and function of the GLP-1 signal in heart failure remains unclear. We investigated the impact of the cardio-intestinal association on hypertensive heart failure using miglitol, an α-glucosidase inhibitor known to stimulate intestinal GLP-1 production. Methods and results Dahl salt-sensitive (DS) rats fed a high-salt diet were assigned to miglitol, exendin (9-39) (GLP-1R blocker) and untreated control groups and treated for 11 weeks. Control DS rats showed marked hypertension and cardiac dysfunction with left ventricular dilatation accompanied by elevated plasma GLP-1 levels and increased cardiac GLP-1R expression as compared with age-matched Dahl salt-resistant (DR) rats. Miglitol further increased plasma GLP-1 levels, suppressed adverse cardiac remodelling, and mitigated cardiac dysfunction. In cardiomyocytes from miglitol-treated DS hearts, mitochondrial size was significantly larger with denser cristae than in cardiomyocytes from control DS hearts. The change in mitochondrial morphology reflected enhanced mitochondrial fusion mediated by protein kinase A activation leading to phosphorylation of dynamin-related protein 1, expression of mitofusin-1 and OPA-1, and increased myocardial adenosine triphosphate (ATP) content. GLP-1R blockade with exendin (9-39) exacerbated cardiac dysfunction and led to fragmented mitochondria with disarrayed cristae in cardiomyocytes and reduction of myocardial ATP content. In cultured cardiomyocytes, GLP-1 increased expression of mitochondrial fusion-related proteins and ATP content. When GLP-1 and exendin (9-39) were administered together, their effects cancelled out. Conclusions Increased intestinal GLP-1 secretion is an adaptive response to heart failure that is enhanced by miglitol. This could be an effective strategy for treating heart failure through regulation of mitochondrial dynamics.

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